Specific Knockout of Notch-1 Attenuates Non-alcoholic Fatty Liver Disease by Promoting SHP2 Phosphorylation

Overview

Journal Aging (Albany NY)

Specialty Geriatrics

Date 2023 Dec 14

PMID 38095642

Authors

Qian Gao

Yonggang Lu

Weiling Zhou

Affiliations

Soon will be listed here.

Abstract

Objective: To investigate the effect of Notch-1 signaling on NAFLD and its molecular mechanism.

Methods: The lipid deposition in liver tissues was detected by oil red O staining. Western blotting was performed to detect the expressions of SREBP1C, SREBP2, LXR, IL-1β, IL-18, NLRP3, Notch-1, NOX2, NOX4, p-PI3K and p-SHP2 in macrophages, and the expressions of ALIX, CD9, IL-1β and SREBP1C in exosomes. Macrophages in the Notch-1 group and Notch-1 group were treated with FFA, and those in the Notch-1+FFA group and Notch-1+FFA group were treated with SHP2 inhibitors PHPS1 and Relaxin.

Results: It was observed by oil red O staining that lipid deposition in mice with NAFLD was reduced in the Notch-1 group. The results of Western blotting showed that the expressions of ALIX, CD9, IL-1β and SREBP1C in macrophage exosomes were significantly lower in the Notch-1 group than in the Notch-1 group. In macrophages, the expressions of SREBP1C, SREBP2, LXR, IL-1β, IL-18, Notch-1, NOX2, NOX4 and p-PI3K significantly decreased, while the expression of p-SHP2 significantly increased in the Notch-1 group compared with the Notch-1 group. The Notch-1+FFA group had significantly decreased expressions of SREBP1C, NLRP3, IL-1β, IL-18, SREBP2, NOX2, NOX4 and p-PI3K and a significantly increased expression of p-SHP2 compared with the Notch-1+FFA group. However, the differences in the above proteins were all eliminated after PHPS1 and Relaxin were added.

Conclusion: Specific knockout of Notch-1 attenuates NAFLD, and reduces inflammation and lipid deposition in the liver by promoting SHP2 phosphorylation.

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PMID: 39101141 PMC: 11294207. DOI: 10.3389/fphar.2024.1423903.

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